Marrow transplants can reverse adult sickle cell

Thursday, July 3, 2014

CHICAGO (AP) — Bone marrow transplants can reverse severe sickle cell disease in adults, a small study by government scientists found, echoing results seen with a similar technique used in children.

The researchers and others say the findings show age need not be a barrier and that the technique may change practice for some adult patients when standard treatment fails.

The transplant worked in 26 of 30 adults, and 15 of them were even able to stop taking drugs that prevent rejection one year later.

"We're very pleased," said Dr. John Tisdale, the study's senior author and a senior investigator at the National Institutes of Health. "This is what we hoped for."

The treatment is a modified version of bone marrow transplants that have worked in kids. Donors are a brother or sister whose stem cell-rich bone marrow is a good match for the patient.

Tisdale said doctors have avoided trying standard transplants in adults with severe sickle cell disease because the treatment is so toxic. Children can often tolerate it because the disease typically hasn't taken as big a toll on their bodies, he said.

The disease is debilitating and often life-shortening; patients die on average in their 40s, Tisdale said. That's one reason why the researchers decided to try the transplants in adults, with hopes that the technique could extend their lives.

The treatment involves using chemotherapy and radiation to destroy bone marrow before replacing it with healthy donor marrow cells. In children, bone marrow is completely wiped out. In the adult study, the researchers only partially destroyed the bone marrow, requiring less donor marrow. That marrow's healthy blood cells outlast sickle cells and eventually replace them.

Sickle cell disease is a genetic condition that damages oxygen-carrying hemoglobin in red blood cells, causing them to form abnormal, sickle shapes that can block blood flow through the veins. It can cause anemia, pain and organ damage. The disease affects about 100,000 Americans, mostly blacks, and millions worldwide.

Results from the adult study, involving patients aged 29 on average, were published Tuesday in the Journal of the American Medical Association. The usual treatment hadn't worked, a drug called hydroxyurea, and they had transplants at an NIH research hospital in Bethesda, Maryland.

The treatment failed to reverse sickle cell in four of the 30 patients and one died of a disease-related complication. Another patient died suddenly a few weeks ago — an elderly man whose transplant four years ago had been a success. Tisdale said that man had lived longer than the normal lifespan for sickle cell patients but that his death was unexpected and an autopsy was to be performed.

The researchers are unsure why the technique didn't work for everyone but they note that most patients survived more than three years on average, and some patients from an early phase of the study have been off anti-rejection drugs for more than seven years.

Tisdale said based on the latest results, adults with severe disease should be offered transplants if drug treatment doesn't work. One limitation is that fewer than 1 out of 4 adults with sickle cell disease likely have siblings who would be a good match. But Tisdale said NIH scientists are studying whether relatives who aren't as close a match would also be suitable donors.

A JAMA editorial by blood specialists at Washington University in St. Louis said the study shows that limiting the transplants to children should be reconsidered.

"These findings offer hope," Drs. Allison King and John DiPersio wrote in the editorial.